There is considerable overlap between the cognitive deficits observed in humans with frontal lobe damage and those described in patients with Parkinson's disease. Similar frontal impairments have been found in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) primate model of Parkinsonism. Here we provide quantitative documentation of the cognitive, oculomotor, and skeletomotor dysfuncti...

The dithiol reagents phenylarsine oxide (PAO) and dibromobimane (DBrB) have opposite effects on the F 1 O -ATPase activity. PAO 20% increases ATP hydrolysis at 50 μM when enzyme activity is activated by natural cofactor Mg 2+ 150 it Ca . PAO-driven activation reverted to basal dithiothreitol (DTE). Conversely, 300 DBrB decreases 25% 50% In both cases, inhibition insensitive DTE. mitochondrial p...

Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA a...

Urocortin (UCN) protects hearts against ischemia and reperfusion injury whether given before ischemia or at reperfusion. Here we investigate the roles of PKC, reactive oxygen species, and the mitochondrial permeability transition pore (MPTP) in mediating these effects. In Langendorff-perfused rat hearts, acute UCN treatment improved hemodynamic recovery during reperfusion after 30 min of global...

The chemokine CX3CL1/fractalkine is expressed by neurons as a transmembrane-anchored protein that can be cleaved to yield a soluble isoform. However, the roles for these two types of endogenous CX3CL1 in neurodegenerative pathophysiology remain elusive. As such, it has been difficult to delineate the function of the two isoforms of CX3CL1, as both are natively present in the brain. In this stud...

The aim of the present study was to investigate the effect of Scutellaria baicalensis stem-leaf total flavonoid (SSTF) on the dopaminergic neurons in the substantia nigra in a mouse model of Parkinson's disease (PD). The mouse model was established by intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). SSTF (5 mg/kg) was administered to the mice before or after MPTP in...

The parkinsonian-inducing compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is converted by isolated hepatocytes to its primary metabolite, the 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPDP+), and to its fully oxidized derivative, 1-methyl-4-phenylpyridinium ion (MPP+). Only the latter, however, accumulates in the cells. Incubation of hepatocytes in the presence of MPDP+ also res...

The aims of this study were to investigate the effect of chinonin in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice and to examine the possible mechanisms. The neurotoxin MPTP was employed to create a subacute Parkinson's disease (PD)-like model in C57BL/6 mice. Chinonin (10, 20, 40 mg/kg body weight) was intraperitoneally administered 0...

Cyclooxygenase (COX) isoenzyme is known to play an important role in the pathophysiology of Parkinson's disease. The present study evaluated the neuroprotective effect of nimesulide, a preferential COX-2-inhibitor against 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP)-model of Parkinson's disease. Intrastriatal administration of MPTP (32 micromol in 2 microl) produced a significant decreas...

Caffeine and more specific antagonists of the adenosine A(2A) receptor recently have been found to be neuroprotective in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Here we show that 8-(3-chlorostyryl)caffeine (CSC), a specific A(2A) antagonist closely related to caffeine, also attenuates MPTP-induced neurotoxicity. Because the neurotoxicity of MPTP rel...